Retinal Peptide Formulation for Aqueous Intravitreal Delivery
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing peptide compositions, such as Met-12, are difficult to formulate in aqueous solutions suitable for intravitreal injection due to poor solubility and require low pH conditions, leading to potential ocular toxicity and significant loss of potency, necessitating the development of easy-to-formulate, non-toxic peptide formulations for protecting retinal cells from extrinsic pathway-mediated apoptosis.
Innovation Solution
Development of biologically active, aqueous formulations of a C-terminal amide peptide (Compound 1) or its pharmaceutically acceptable salts, specifically formulated for ocular delivery, using non-ionic surfactants and organic cosolvents to enhance solubility and stability, allowing for effective protection of retinal cells from Fas- and TRAIL-mediated apoptosis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If existing peptide compositions (e.g., Met-12) are formulated in aqueous solutions, then they can be administered intravitreally, but they require low pH conditions which cause ocular toxicity and loss of potency
Solution Approach 1:
The patent modifies the peptide structure by C-terminal amidation and creates salt forms (acetate, trifluoroacetate, hydrochloride) to change the chemical parameters of the peptide, enabling formulation at physiological pH ranges (3.0-7.0) without requiring the low pH conditions that caused toxicity with previous formulations
Solution Approach 2:
The patent combines the modified peptide with non-ionic surfactants (polysorbates, poloxamers) and organic cosolvents (propylene glycol, dimethyl sulfoxide) to create composite formulations that enhance solubility and stability while maintaining biocompatibility and avoiding ocular toxicity
2Stability of the object's composition
If existing peptide compositions are formulated with low pH conditions, then they maintain peptide stability, but they cause significant loss of potency and ocular toxicity
Solution Approach 1:
The patent changes the peptide's chemical parameters through C-terminal amidation and salt formation, which fundamentally alters the pH-stability relationship. The modified peptide maintains stability at physiological pH ranges (3.0-7.0) without requiring the low pH conditions that previously caused both stability and potency issues
Solution Approach 2:
The patent introduces non-ionic surfactants and organic cosolvents as intermediary substances that mediate between the peptide and aqueous environment, enhancing peptide stability through micellar encapsulation and solvation while maintaining potency and avoiding the need for low pH conditions
3Quantity of substance
If Compound 1 is formulated with non-ionic surfactants and organic cosolvents, then solubility and stability are enhanced, but formulation complexity increases
Solution Approach 1:
The patent modifies the peptide's physical and chemical parameters through C-terminal amidation and salt formation, which inherently improves solubility and stability characteristics, reducing the need for complex formulation strategies and allowing simpler formulation approaches
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Compound 1 demonstrates at least 10-fold greater potency than Met-12 in inhibiting caspase 8 activation and protecting photoreceptor cells in vitro and in vivo, with clinically acceptable formulations, effectively preventing retinal cell death and preserving vision.
Implementation Method 1
using non-ionic surfactants and organic cosolvents to enhance solubility and stability
Implementation Method 2
using non-ionic surfactants and organic cosolvents to enhance solubility and stability
Data Source
AI summary
Provided herein are compositions including peptides, pharmaceutical preparations thereof, and methods of preventing photoreceptor death therewith and protecting retina cells, including, but not limited to, photoreceptors and retinal pigment epithelium, from Fas- or TRAIL-mediated apoptosis.